PROJECT DESCRIPTION: We request renewed support for a postdoctoral training program focused on molecular mechanisms of immunologic tolerance and autoimmunity. The application comes from a highly interactive faculty centered in the Integrated Department of Immunology whose faculty is strongly focused on B and T cell development, antigen recognition, repertoire development, silencing by editing, deletion and anergy, and understanding autoimmunity. The Integrated Department of Immunology is comprised of 65 faculty (primary and secondary) from three institutions: the National Jewish Health, The Barbara Davis Center for Childhood Diabetes (BDC) and The University of Colorado School of Medicine. Nearly half of the 20 training faculty have been recruited to the Department since its inception in 1999, and all training faculty are supported by NIH RO1 grants on which they are Principal Investigator. We request stipend support for 4 fellows who will train in laboratories of their choosing whose research is focused of immune tolerance and autoimmunity. The fellows will participate in regularly scheduled journal clubs, research in progress seminars, formal seminars and courses, e.g. on ethics and survival skills in science, and their progress will be monitored by a training oversight committee (TOC). Trainees will be appointed for one year and reappointed only if they are judged by the TOC to be making significant progress. Our goal is to provide fellows with comprehensive knowledge of immune tolerance and mouse models of autoimmunity, and sufficient understanding of clinical autoimmunity to enable their development of productive clinical collaborative ties for translation of research. The Program Director is Dr. John Cambier, Ida and Cecil Green Distinguished Professor and Chairman of the Integrated Department of Immunology. Dr. Cambier is an expert in B cell signaling, activation and anergy, and has trained in excess of 60 graduate students and postdoctoral fellows. The training program has available superb research facilities and the faculty, are interactive in both training and research. Although the Denver immunology community has been training pre- and postdoctoral fellows for over 30 years, formation of the Integrated Department of Immunology and hiring of new faculty has provided a strongly uniting influence, and injected new excitement and vitality into our educational and research activities. This training program is a central focus of that vitality.